Ap­ta­hem – a Swedish biotech aim­ing to win the race against sep­sis

In the fight to save a per­son af­fect­ed by sep­sis every sec­ond counts – each hour that pass­es in­creas­es the risk of death with 8 per­cent. It is lit­er­al­ly a race against time, a race that the health­care ser­vices all but too of­ten lose. How­ev­er, Swedish biotech Ap­ta­hem are de­vel­op­ing an emer­gency treat­ment to bet­ter the odds and pre­vent the mas­sive or­gan fail­ure that leads to the deaths of mil­lions of sep­sis pa­tients glob­al­ly each year.

Sep­sis is the world’s third largest cause of death and the lead­ing cause of death for in­fants and chil­dren. The mor­tal­i­ty rates are some­where be­tween 20 to 50 per­cent – for pa­tients who de­vel­op se­vere sep­sis as high as 80 per­cent. In the US alone ap­prox­i­mate­ly 400,000 peo­ple die from sep­sis every year, mak­ing the con­di­tion dead­lier than breast, colon, and lung can­cer com­bined.

Sep­sis is the body’s re­sponse to an in­fec­tion, most com­mon­ly a bac­te­r­i­al in­fec­tion. But it is an ex­treme re­sponse that can over­load the or­gans and lead to death. Sep­sis can start with some­thing as mun­dane as a scraped el­bow or a cut fin­ger. Through this wound bac­te­ria can en­ter the body which then re­sponds by re­leas­ing chem­i­cals in­to the blood stream to fight the in­fec­tion. But the in­flam­ma­to­ry re­sponse that is trig­gered by these chem­i­cals can lead to tis­sue dam­age, or­gan fail­ure and death. When the sep­sis wors­ens, the blood flow to vi­tal or­gans is in­hib­it­ed, mean­ing that blood clots can form. In the most se­vere cas­es of sep­sis the blood pres­sure drops, and mul­ti­ple or­gan fail­ure en­sues. In these cas­es, the pa­tient quick­ly dies from sep­tic shock.

There is lit­tle doubt that sep­sis rep­re­sents a large un­met clin­i­cal need – the mar­ket is sig­nif­i­cant as are the treat­ment costs. In the US sep­sis treat­ment is es­ti­mat­ed at 14.6 bil­lion USD an­nu­al­ly and in 2014 sep­sis was named as the most ex­pen­sive in-pa­tient cost in Amer­i­can hos­pi­tals, av­er­ag­ing more than 18 000 USD per hos­pi­tal stay. A re­port from Glob­al Da­ta pre­dicts that the sep­sis and sep­tic shock mar­ket across the sev­en ma­jor phar­ma­ceu­ti­cal mar­kets (US, France, Ger­many, Italy, Spain, the UK, and Japan), will grow to 5.9 bil­lion USD by 2026. This rep­re­sents a com­pound an­nu­al growth rate (CA­GR) of 7.9%.

For sev­er­al years, R&D in sep­sis has been a rather bar­ren field and it has been a long time since a new sep­sis treat­ment reached the mar­ket. At present, the on­ly treat­ment avail­able to sep­sis pa­tients is an­tibi­otics, IV flu­ids and adren­a­line to con­trol to blood pres­sure. This might seem sur­pris­ing as sep­sis is such a sig­nif­i­cant killer, but the lack of new treat­ments is con­nect­ed to the high bar that the FDA has set for ap­proval as well as the high cost of treat­ment. How­ev­er, as re­port­ed by End­points News, the FDA has be­gun to low­er the bar in re­cent years, which could open up the mar­ket for new sep­sis treat­ments.

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Aim­ing for the huge sep­sis mar­ket is Swedish biotech Ap­ta­hem with its new ap­proach to de­feat­ing sep­sis. The com­pa­ny’s lead can­di­date, Ap­ta-1, is be­ing de­vel­oped as an emer­gency drug to pre­vent the dam­age of or­gans and tis­sues caused by sep­sis.  Where cur­rent treat­ments are un­able to coun­ter­act the wide spec­trum of re­ac­tions that sep­sis pa­tients can ex­hib­it, Ap­ta-1 has shown po­ten­tial to counter these re­ac­tions.

Ap­ta­hem was found­ed in 2014 in Malmö but the com­pa­ny’s tech­nol­o­gy is in fact based on 17 years of re­search car­ried out at Lund Uni­ver­si­ty in co-op­er­a­tion with Karolin­s­ka In­sti­tutet and the Swedish In­sti­tute for Com­mu­ni­ca­ble Dis­ease Con­trol. This re­search re­sult­ed in the de­vel­op­ment of three syn­thet­ic bio­mol­e­cules with the SE­LEX ap­tamer method. These ap­tamers were tar­get­ing a bind­ing pro­tein in­duced by brain malar­ia to bind red blood cells for the prop­a­ga­tion of the malar­ia par­a­site.

Luiza Jedli­na, CSO Ap­ta­hem

Ap­tamers are oligonu­cleotides, short RNA se­quences that bind to a spe­cif­ic tar­get mol­e­cule and im­i­tates an­ti­bod­ies. How­ev­er, the ap­tamers al­so have cer­tain char­ac­ter­is­tics mak­ing them par­tic­u­lar­ly in­ter­est­ing to phar­ma­ceu­ti­cal re­search. They have a low im­muno­genic­i­ty and have a po­ten­tial to be man­u­fac­tured in large scale at pre­dict­ed low­er cost com­pared to an­ti­body man­u­fac­tur­ing.

When study­ing how the se­lect­ed ap­tamers func­tioned with brain malar­ia, which is 100 % dead­ly, the re­searchers dis­cov­ered that they ap­peared to have the abil­i­ty to dis­solve and in­hib­it blood clots and thus pre­vent a build up for an in­duced stroke. Ap­ta­hem’s cur­rent CSO, Luiza Jedli­na, re­al­ized the po­ten­tial of the dis­cov­ery – ap­tamers could be used to treat a va­ri­ety of co­ag­u­la­tion dis­or­ders. Ap­ta­hem chose to fo­cus on un­der­stand­ing how an ex­ist­ing mol­e­cule could be ap­plied in med­ical treat­ment. Their method is based on how Plas­mod­i­um fal­ci­parum, a par­a­site caus­ing malar­ia, pro­duces pro­teins and us­es them to weak­en the body’s de­fens­es.  These pro­teins have a neg­a­tive ef­fect on e.g. co­ag­u­la­tion, the an­ti-in­flam­ma­to­ry sys­tem and the im­mune sys­tem which helps the par­a­site sur­vive.

It is this mul­ti-ef­fect that has in­spired Ap­ta­hem’s pipeline. The com­pa­ny’s drug can­di­dates (Ap­ta-1, Ap­ta-2 and Ap­ta-3) aim to af­fect sev­er­al as­pects of the hu­man body but in­stead of hav­ing a neg­a­tive ef­fect the ap­tamers should strength­en co­ag­u­la­tion, the an­ti-in­flam­ma­to­ry sys­tem and the im­mune sys­tem. For sep­sis this means that ap­tamers, un­like to­day’s treat­ments, rep­re­sent an op­por­tu­ni­ty to coun­ter­act the wide spec­trum of phys­i­cal re­ac­tions that pa­tients ex­hib­it.

With re­gards to fi­nanc­ing, Ap­ta­hem an­nounced in June of this year that it had en­tered in­to an is­suance agree­ment with YA II PN Ltd, a fund rep­re­sent­ed by U.S.-based Yorkville Ad­vi­sors Glob­al.

If the whole com­mit­ment is ex­er­cised, the agree­ment means that Ap­ta­hem has se­cured fi­nanc­ing of up to 20 MSEK dur­ing a 36-month pe­ri­od. The agree­ment in­cludes 25 con­vert­ibles of which 2 so far has been is­sued.

In or­der to fur­ther strength­en its fi­nan­cial sit­u­a­tion, Ap­ta­hem re­cent­ly con­clud­ed a fi­nanc­ing round that will add a fur­ther 25.4 MSEK (pri­or to rights is­sue costs) to the com­pa­ny cof­fers.  The fi­nanc­ing round did not quite reach the goal Ap­ta­hem had set but the com­pa­ny can look for­ward to an ex­cit­ing 2019 nonethe­less.

The com­pa­ny plans to start phase I stud­ies with Ap­ta-1 dur­ing Q3 2019 and when ad­vanc­ing to clin­i­cal stud­ies the com­pa­ny can lean on some very en­cour­ag­ing re­sults from pre-clin­i­cal tri­als. The tox­i­col­o­gy- and safe­ty stud­ies showed very good re­sults and in No­vem­ber 2018 Ap­ta­hem could al­so an­nounce pos­i­tive re­sults from an ex­plorato­ry study in pri­mates. This has sig­nif­i­cant­ly in­creased the hope of show­ing good ef­fi­ca­cy in the up­com­ing, more ex­ten­sive con­fir­ma­to­ry stud­ies and fur­ther on hu­man stud­ies.

In the longer term Ap­ta­hem’s strat­e­gy is to es­tab­lish part­ner­ships or li­cens­ing agree­ments that would help bring Ap­ta-1 to mar­ket and to the mil­lions of peo­ple who are af­fect­ed by sep­sis every year.

Read more about Ap­ta­hem here.

Im­age cred­it: Shut­ter­stock